The tumor-associated antigen MUC-1, or DF-3/MUC-1, is overexpressed on the cell surface of many human adenocarcinomas such as ovarian, breast, pancreas, colorectal and prostate carcinoma, and hematological malignancies including multiple myeloma and some B-cell non-Hodgkin lymphomas. While MUC-1 is expressed on some normal epithelial tissue on lumenal surfaces, it has been demonstrated that the apical localization of MUC-1 is lost in tumor tissues. In addition, MUC-1 is under-glycosylated in human adenocarcinomas as compared with normal tissues and thus the antigenic epitopes of the protein core are more exposed. A high level of MUC-1 expression and secretion has also been shown to be associated with poor prognosis and high metastatic potential. It was initially demonstrated that histocompatibility complex (MHC)-unrestricted cytotoxic T cells could be established from subjects with pancreatic carcinoma, ovarian cancer and multiple myeloma; these T cells were shown to recognize the MUC-1 protein core in the 20 amino acid variable number of tandem repeat (VNTR)2 region. While the VNTR region is immunogenic for MHC non-restricted CTL as well as for the production of MUC-1 specific antibodies, relatively limited information is available with respect to the immunogenicity of the region outside the VNTR.
Current treatment of cancers include radiation therapy and chemotherapy, which have particularly adverse effects on a subject undergoing such therapies.
Accordingly, there is a need for improved, safer treatments that have long-lasting protective effects for the prevention and treatment of tumors. In particular, there is a need for treatments that are more specific and less toxic than the currently available therapeutic agents.